A defined tuberculosis vaccine candidate boosts BCG and protects against multidrug-resistant Mycobacterium tuberculosis.
A defined tuberculosis vaccine candidate boosts BCG and protects against multidrug-resistant Mycobacterium tuberculosis.
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DOI：
10.1126/scitranslmed.3001094
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发表时间：
2010-10-13
影响因子：
17.1
通讯作者：
Reed SG
中科院分区：
文献类型：
--
作者：
Bertholet S;Ireton GC;Ordway DJ;Windish HP;Pine SO;Kahn M;Phan T;Orme IM;Vedvick TS;Baldwin SL;Coler RN;Reed SG
尽管卡介苗（BCG）儿童疫苗的广泛使用，结核病（TB）仍然是一个严重的全球性健康问题。一个成功的结核病疫苗，取代或加强卡介苗将包括抗原，诱导或召回适当的T细胞反应。四个结核分枝杆菌（Mtb）抗原，包括毒力因子家族PE/PPE和EsX的成员，或与潜伏期相关的抗原作为一个单一的重组融合蛋白。当与佐剂GLA-SE（一种稳定的水包油纳米乳剂）一起施用时，融合蛋白ID 93在小鼠、豚鼠和食蟹猴中具有免疫原性。在小鼠中，ID 93/GLA-SE组合诱导多功能CD 4 TH 1-细胞应答，其特征在于抗原特异性IFN-γ、肿瘤坏死因子和白介素-2，以及随后感染毒性或多药耐药Mtb菌株的动物肺中细菌数量的减少。此外，用ID 93/GLA-SE加强BCG接种的豚鼠导致病理学减少和杆菌减少，并防止用毒性Mtb攻击的动物死亡。最后，ID 93在BCG接种或Mtb暴露的人外周血单核细胞中引起多功能效应CD 4和CD 8 T细胞应答。本研究确定了蛋白亚单位疫苗ID 93/GLA-SE在动物中保护免受TB和MDR-TB，并且是增强儿童BCG疫苗的保护效力的候选物。
Despite the widespread use of Mycobacterium bovis bacillus Calmette-Guerin (BCG) childhood vaccine, tuberculosis (TB) remains a serious global health problem. A successful vaccine against TB that replaces or boosts BCG will include antigens that induce or recall appropriate T cell responses. Four Mycobacterium tuberculosis (Mtb) antigens, including members of the virulence factor families PE/PPE and EsX, or antigens associated with latency were produced as a single recombinant fusion protein. When administered with the adjuvant GLA-SE, a stable oil-in-water nanoemulsion, the fusion protein ID93 was immunogenic in mice, guinea pigs, and cynomolgus monkeys. In mice, ID93/GLA-SE combination induced polyfunctional CD4 TH1-cell responses characterized by antigen-specific IFN-gamma, tumor necrosis factor and interleukin-2, as well as a reduction in the number of bacteria in the lungs of animals subsequently infected with virulent or multidrug resistant Mtb strains. Furthermore, boosting BCG-vaccinated guinea pigs with ID93/GLA-SE resulted in reduced pathology and fewer bacilli, and prevented the death of animals challenged with virulent Mtb. Finally, ID93 elicited polyfunctional effector CD4 and CD8 T-cell responses in BCG-vaccinated or Mtb-exposed human peripheral blood mononuclear cells. This study establishes that the protein subunit vaccine ID93/GLA-SE protects against TB and MDR-TB in animals, and is a candidate for boosting the protective efficacy of the childhood BCG vaccine.
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影响因子：
5.5
作者：
Velez, Ivan D.;Gilchrist, Katherine;Piazza, Franco M.
通讯作者：
Piazza, Franco M.
影响因子：
4.4
作者：
Dietrich, Jes;Billeskov, Rolf;Andersen, Peter
通讯作者：
Andersen, Peter
影响因子：
5.8
作者：
Anderson, Ryan C.;Fox, Christopher B.;Vedvick, Thomas S.
通讯作者：
Vedvick, Thomas S.
影响因子：
158.5
作者：
SMALL, PM;SHAFER, RW;SCHOOLNIK, GK
通讯作者：
SCHOOLNIK, GK
DOI：
10.4161/hv.8570
发表时间：
2009-07-01
期刊：
HUMAN VACCINES
影响因子：
--
作者：
Von Eschen, Kenneth;Morrison, Royce;Ballou, W. Ripley
通讯作者：
Ballou, W. Ripley